Drug and alcohol abuse and dependency, along with all of the medical and behavioral complications of drug abuse, ranging from hepatitis B and delta, cirrhosis and AIDS to psychiatric disorders and sociopathic behaviors, are the major medical problems confronting our nation and the world today. Effective treatments, based on fundamental knowledge about the drugs of abuse, pharmacologic agents used in the treatment of drug abuse, and the biological bases of addictive disease, as well as information about and approaches to the management of medical and behavioral problems which may complicate treatment, are needed urgently. Heroin abuse continues to afflict over 2 million persons at this time, with over one-half million "hard-core" heroin addicts in the United States, constituting the greatest numbers of patients in the second highest risk group for AIDS. Cocaine abuse continues to escalate, with around 6 million persons now reported to be regular users of cocaine and with increasing numbers using the more potent free-base form, "crack". The central theme of the proposed Center will be to identify and study the biological correlates of treatment of addictions, and as a major part of this effort, to study in depth several factors which may negatively, and also positively, affect treatment outcome. Problems such as medical and behavioral including pharmacological, metabolic and behavioral aspects of treatments, will be studied. In addition, some studies will attempt to elucidate further the biological bases of addictive diseases, with the goal of developing in the future novel, improved or more specific pharmacological as well as behavioral approaches for the treatment of various addictions. To the same end, with the goal of developing new or modifying existing treatments to improve both short- and long-term treatment outcome, studies are proposed to delineate the effects of existing treatments on those aspects of physiology which may by intrinsically involved with the addictive disease process, or which may, by inadvertent alterations of physiology, contribute to treatment failure. In the proposed Center, studies of basic science, basic clinical research, and applied clinical research types will all be focused on the central theme of studying the biological correlates of the treatment of addiction. These various scientific approaches will be integrated through the Core Resources and other interactions which only a Center can appropriately provide.